Research Summary

Darryl C. Zeldin, M.D., is NIEHS Scientific Director, head of the Environmental Cardiopulmonary Disease Group, and holds a secondary appointment in the Clinical Research Branch. The group conducts basic and clinical/translational research to better understand the role of the environment in the etiology and pathogenesis of respiratory and cardiovascular diseases such as allergy, asthma, adult respiratory distress syndrome, pulmonary fibrosis, atherosclerosis, hypertension, ischemic heart disease, and stroke.

The group has a major research interest in eicosanoids, with an emphasis on how they function in the respiratory and cardiovascular systems. The group has identified a family of cytochrome P450 enzymes that are abundant in cardiovascular tissues and active in the metabolism of arachidonic acid to epoxyeicosatrienoic acids (EETs), which are potent vasodilators and cardiovascular protective agents. To study the effects of altered expression of cytochromes P450 on cardiovascular function, the group developed several new transgenic knockout mouse models.

Opportunities for translational research in this area include development of new drugs for blood pressure control, atherosclerosis and ischemic heart disease. Identification of individuals at increased risk for these disorders due to P450 genetic variation may also lead to new approaches to disease prevention.

The group has also conducted studies to examine the role of cyclooxygenases in lung function and disease. The work, based on the hypothesis that cyclooxygenase-derived eicosanoids (prostaglandins) are important modulators of the lung immune response to environmental agents, such as allergens and bacterial lipopolysaccharide, involves development and phenotypic characterization of new transgenic knockout mouse models. This research will lead to additional opportunities for mechanistic and translational research in a variety of inflammatory lung diseases.

In addition, the group studies basic mechanisms, which underlie sex differences in the response of the lung to environmental agents, such as indoor allergens, bacterial lipopolysacchride, respiratory viruses and pro-fibrotic agents.

Lastly, the group is active in clinical research on asthma and the environment. The group's research focuses on indoor allergen exposures, and other potential risk factors and modifying factors (e.g. endotoxin), which are associated with the development and exacerbation of allergic respiratory diseases. The group has conducted large national studies which have not only resulted in a better understanding of the characteristics and predictors of indoor allergen and endotoxin exposures in U.S. households, but also have provided information on the importance of different allergens in asthma and other allergic diseases that are of significant public health concerns nationally and globally. The main goal of the group is to provide sound scientific basis for the development and implementation of environmental interventions that will be effective in preventing asthma and other allergic diseases.

Current projects:

Understanding the role of cytochrome P450-derived eicosanoids in cardiovascular homeostasis and in the pathogenesis of cardiovascular diseases such as atherosclerosis, hypertension, ischemic heart disease, and stroke

Elucidating the role of cyclooxygenase-derived eicosanoids in lung function and disease

Examining the basic mechanisms for sex differences in the response of the lung to a variety of environmental agents such as indoor allergens, bacterial lipopolysacchride, respiratory viruses and pro-fibrotic agents

Determining the prevalence and determinants of indoor allergen and endotoxin exposures and investigating the complex relationships between those exposures, allergic sensitization, and the development and exacerbation of allergic diseases, including asthma

Zeldin earned a B.A. in chemistry from Boston University in 1982 and an M.D. from Indiana University School of Medicine in 1986. He completed a Residency in Internal Medicine at Duke University in 1989 and a Fellowship in Pulmonary/Critical Care Medicine at Vanderbilt University in 1993. Zeldin, a physician-scientist who is internationally recognized for his contributions to the fields of environmental health, respiratory disease and cardiovascular disease, is a member of the American Society for Clinical Investigation (ASCI), a Fellow in the American College of Chest Physicians and a Fellow in the American Heart Association. He has served on NIH and foundation study sections and is a member of the editorial boards of several scientific journals. He has published over 200 peer-reviewed articles in leading biomedical journals, as well as numerous reviews and book chapters. Zeldin is on staff at Duke University Medical Center, where he serves as an attending physician on the pulmonary consult service and the medical intensive care unit. He served as the NIEHS Acting Clinical Director from 2007-2011 and currently serves as the NIEHS Scientific Director.